Research ArticleHypertension

Intestinal Inhibition of the Na+/H+ Exchanger 3 Prevents Cardiorenal Damage in Rats and Inhibits Na+ Uptake in Humans

Science Translational Medicine  12 Mar 2014:
Vol. 6, Issue 227, pp. 227ra36
DOI: 10.1126/scitranslmed.3007790

You are currently viewing the editor's summary.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Pass the Salt

Whether life arose on earth or elsewhere, our ancestors certainly spent some time in the Earth’s oceans: We still carry the evidence for that in the saltiness of our bodily fluids. When the salty balance of our body goes awry (through diet, for example), disease can result. Now, Spencer and colleagues have found a way to prevent the absorption of dietary sodium through the intestine without requiring the drug be present throughout the body, a safer approach.

Normally, most of the sodium chloride that is consumed is taken up by a dedicated transporter in the membranes of intestinal cells. This sodium-proton exchanger, NHE3, pumps one sodium ion in and one proton out, bringing dietary sodium into the body. The authors used an NHE3 inhibitor called tenapanor that does not cross the intestinal barrier. They tested its effects on sodium uptake in normal rats and normal healthy humans, as well as in a rat model of salt-driven hypertension that resembles the patients that might benefit from this treatment.

In healthy humans and rats, tenapanor decreased sodium uptake from the intestine and increased its concentrations in the stool, as expected for an NHE3 inhibitor acting exclusively in the intestine. It had no other damaging effects to the animals or subjects. The rats with salt-driven hypertension exhibited numerous problems—heart hypertrophy, excess fluid, arterial stiffening, and high blood pressure. Treatment with the drug before the disease onset and—important for a therapeutic agent—after disease onset improved all of these measures.

A combination of tenapanor and the popular antihypertensive drug enalapril (which acts to inhibit angiotensin-converting enzyme) was more effective against certain outcomes than either drug alone. The combination improved cardiac function (left ventricular hypertrophy and arterial stiffness) and kidney function markedly, which enalapril alone did not.

Modern humans often eat too much salt or have other reasons to limit the amount of sodium they consume. The inhibition of sodium uptake transporters in the intestine may prove a better way to combat these problems than our current approaches.